Blood flow can signal during angiogenesis not only through mechanotransduction, but also by affecting growth factor distribution
Blood flow can signal during angiogenesis not only through mechanotransduction, but also by affecting growth factor distribution
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DOI：
10.1007/s10456-017-9553-x
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发表时间：
2017-08-01
期刊：
影响因子：
9.8
通讯作者：
Jones, Elizabeth A. V.
中科院分区：
文献类型：
--
作者：
Ghaffari, Siavash;Leask, Richard L.;Jones, Elizabeth A. V.
生长因子，如VEGF，促进新血管的发芽。生长因子通常在远离内皮细胞的地方产生，这些蛋白质的运输通常被认为是通过扩散发生的。然而，当在灌注的血管床中发芽时，存在可以改变蛋白质运输的间质流动。我们最近开发了一种同时分析鸟类胚胎血流动力学和血管重塑的技术。在这项研究中，我们将我们的技术扩展到通过间充质组织多孔基质的间质流动模型，并利用它来研究血管中的流动如何影响间充质中生长因子的分布，使用VEGF作为原型血管生成分子。我们发现，流量通过机械力的直接作用和对生长因子分布的间接影响来控制发芽位置和伸长。最重要的是，我们发现VEGF的分布受间质血流调节，而VEGF扩散的影响可以忽略不计。
Growth factors, such as VEGF, promote the sprouting of new blood vessels. Growth factors are generally produced far from the endothelium, and the transport of these proteins is often assumed to occur through diffusion. When sprouting occurs in a perfused vascular bed, however, interstitial flow is present that can modify protein transport. We recently developed a technique to analyze flow dynamics and vascular remodeling simultaneously in avian embryos. In this study, we extend our technique to model interstitial flow through the porous matrix of the mesenchymal tissue and use this to investigate how flow in the blood vessels affects the distribution of growth factors in the mesenchyme, using VEGF as a prototypical angiogenic molecule. We find that flow controls sprouting location and elongation, both through the direct action of mechanical force and through indirect effects on growth factor distribution. Most importantly, we find that the distribution of VEGF is regulated by interstitial flow, and the effect of diffusion of VEGF is negligible.